Using genotyping and geospatial scanning to estimate recent mycobacterium tuberculosis transmission, United States

To determine the proportion of reported tuberculosis (TB) cases due to recent transmission in the United States, we conducted a cross-sectional study to examine culture-positive TB cases with complete genotype results (spoligotyping and 12-locus mycobacterial interspersed repetitive unit-variable-number tandem repeat typing) reported during January 2005-December 2009. Recently transmitted cases were defined as cases with matching results reported within statistically significant geospatial zones (identified by a spatial span statistic within a sliding 3-year window). Approximately 1 in 4 TB cases reported in the United States may be attributed to recent transmission. Groups at greatest risk for recent transmission appear to be men, persons born in the United States, members of a minority race or ethnic group, persons who abuse substances, and the homeless. Understanding transmission dynamics and establishing strategies for rapidly detecting recent transmission among these populations are essential for TB elimination in the United States.     

New methods for using computer-aided detection information for the detection of lung nodules on chest radiographs

Objective:

To investigate two new methods of using computer-aided detection (CAD) system information for the detection of lung nodules on chest radiographs. We evaluated an interactive CAD application and an independent combination of radiologists and CAD scores.

Methods:

300 posteroanterior and lateral digital chest radiographs were selected, including 111 with a solitary pulmonary nodule (average diameter, 16 mm). Both nodule and control cases were verified by CT. Six radiologists and six residents reviewed the chest radiographs without CAD and with CAD (ClearRead +Detect™ 5.2; Riverain Technologies, Miamisburg, OH) in two reading sessions. The CAD system was used in an interactive manner; CAD marks, accompanied by a score of suspicion, remained hidden unless the location was queried by the radiologist. Jackknife alternative free response receiver operating characteristics multireader multicase analysis was used to measure detection performance. Area under the curve (AUC) and partial AUC (pAUC) between a specificity of 80% and 100% served as the measure for detection performance. We also evaluated the results of a weighted combination of CAD scores and reader scores, at the location of reader findings.

Results:

AUC for the observers without CAD was 0.824. No significant improvement was seen with interactive use of CAD (AUC = 0.834; p = 0.15). Independent combination significantly improved detection performance (AUC = 0.834; p = 0.006). pAUCs without and with interactive CAD were similar (0.128), but improved with independent combination (0.137).

Conclusion:

Interactive CAD did not improve reader performance for the detection of lung nodules on chest radiographs. Independent combination of reader and CAD scores improved the detection performance of lung nodules.

Advances in knowledge:

(1) Interactive use of currently available CAD software did not improve the radiologists'' detection performance of lung nodules on chest radiographs. (2) Independently combining the interpretations of the radiologist and the CAD system improved detection of lung nodules on chest radiographs.Chest radiography can be considered the workhorse of the radiology department. It is being used for the detection and diagnosis of multiple diseases, including lung nodules, which may represent early lung cancer. Since a chest radiograph is a two-dimensional image, overprojection of multiple anatomical structures is inevitable. This so-called anatomical noise substantially impedes interpretation of chest radiographs. Multiple studies have shown that a substantial amount of lung cancers are missed, ranging from 19% to 26%,^1,2 and even up to 90%.^3–5 More recent studies have shown that the problem of missing lung nodules is still present with the most modern digital radiographic technology.^6,7 Abnormalities can be missed as a result of inadequate search, perception errors or interpretation errors. It has been stated that interpretation by the radiologist is the most important factor for missing lung cancer on chest radiographs.^8,9To reduce miss rates, computer-aided detection (CAD) systems have been developed. Thus far, all studies dealing with chest radiography apply CAD as a second reader to the radiologist, meaning that the CAD marks are made available only after the radiologist has made a primary review. It remains the reader''s discretion to accept or disregard the CAD marks. Results of these studies were contradictory: some found an increased accuracy for the detection of lung nodules,^10–12 whereas other studies reported an increase in sensitivity only at the expense of loss in specificity.^13–16 One problem ameliorating the potential of CAD is the radiologist''s limited ability to reliably discriminate between true-positive (TP) and false-positive (FP) CAD marks.We therefore decided to explore alternative methods of using CAD information. First, we used CAD interactively. In the interactive mode, CAD marks remained hidden unless the radiologist queried a position in the image by clicking with the mouse on that location. If a CAD mark was present in this location, it was shown to the radiologist together with a score of suspicion. Such an interactive CAD system had been shown to be beneficial in chest radiography in an observer study that only used non-radiologists.¹⁷ Second, we computed a mathematical combination of reader and CAD scores. With this method, observers did not need to view the CAD marks at all during their reading of the images, but a mathematical combination of the reader and the CAD scores was computed afterwards. Both methods have been reported to outperform the use of CAD as a second reader for lesion detection in mammograms.^18–20The purpose of this observer study was to test the impact of these two alternative methods of using CAD information on nodule detection on chest radiographs. To optimize baseline performance without CAD, digitally bone-suppressed images (BSIs) were added to the original chest radiographs. BSIs have been shown to improve accuracy for the detection of focal lesions on chest radiographs;^21–24 a further increase in detection performance beyond that of BSIs by adding CAD has also been documented.²⁵     

Plasmapheresis Eliminates the Negative Impact of AAV Antibodies on Microdystrophin Gene Expression Following Vascular Delivery

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.     

Lack of association between the <Emphasis Type="Italic">GRP78</Emphasis> polymorphisms in the promoter and 3' UTR and susceptibility to chronic HBV infection in a Chinese Han population

Background  

Hepatitis B virus (HBV) infection causes large amount of unfolding or false-folding protein accumulation in the endoplasmic reticulum (ER), which in turn induces the expression of glucose-regulated protein 78 (GRP78). The aim in the present study was to analyse the potential association between GRP78 single-nucleotide polymorphisms (SNPs) and the risk of HBV infection.     

Potentially malignant epithelial oral lesions: discrepancies between clinical and histological diagnosis

OBJECTIVE: To evaluate the discrepancy index between the clinical and histological diagnosis and the prevalence of epithelial dysplasia and carcinoma in 45 patients with potentially malignant epithelial oral lesions (PMEL).PATIENTS AND METHODS: We submitted 45 patients with PMEL to clinical examination and obtained a biopsy from each. The results of histological diagnosis were compared to the clinical diagnosis.
RESULTS: Clinical diagnosis showed that the most common PMEL was leukoplakia followed by lichen planus and by actinic cheilitis associated with leukoplakia. The most common site was the buccal mucosa. Histological diagnosis revealed that 46.7% of the PMEL were lichen planus. The discrepancy index between clinical and histological diagnosis was 24.4%. The higher discrepancy index occurred among leukoplakias. The prevalence of epithelial dysplasia and carcinoma was 17.8%.
CONCLUSIONS: We conclude that all PMEL should be submitted to a microscopic analysis because the discrepancy between clinical and histological diagnosis was present in a quarter of these lesionS. Otherwise, the epithelial dysplasia and carcinoma were more frequent in the leukoplakias.     

Severe combined immunodeficiency with abnormalities in expression of the common leucocyte antigen, CD45

Children presenting with disseminated viral infections should be carefully investigated because they almost invariably have an underlying immunodeficiency. A child is reported who had disseminated cytomegalovirus and a novel form of severe combined immunodeficiency with abnormal expression of the common leucocyte antigen, CD45.     

Management of anticoagulated patients in dentoalveolar surgery: a clinical comparative study

This prospective, comparative, clinical study analyzed the postoperative bleeding risk of patients on anticoagulation therapy (AT) who were undergoing toot